things I don't understand (8-10) Flashcards
describe the process of Wnt signalling
- Wnt binds to frizzled and LRP
- LRP’s cytoplasmic tail phosphorylates axin
- the Beta-catenin, GSK3 and APC complex is destabilised = release of beta-catenin
- beta catenin translocates to the nucleus and forms a complex with TCF to activate transcription of target genes
what complex is beta catenin held in by axin
beta-catenin, GSK3 and APC
what does BMP4 inhibit
neural cells - causes them to differentiate into epidermis
what inhibits BMP4 allowing ectodermal cells to differentiate into neural cells
chordin, noggin & follistatin
what happens in mice KO for chordin and noggin
BMPs are not inhibited so neural fate is not induced. produces mice without a forebrain, nose or facial structure
describe the process of neural tube formation
- Neuroectodermal cells dive down and differentiate into the neural plate
- On either side of the neural plate is a band of cells called the neural crest
- Neural plate invaginates and the neural crest tissue sits at the top = forms the neural groove
- Neural groove pinches off to form the neural tube – neural crest cells combine
what do the neural crest go on to produce
neurons of the peripheral nervous system
- depending on positional cues they will become either sympathetic or parasympathetic
what is required for fusion of the neural plate
adhesion molecules - N-CAM and N-cadherin
where do neural stem cells come from
the ventricular zone of the neural tube
what forms radial glia
neuroepithelial cells under the influence of FOXG1/HX2/PAX6
name 2 Wnt inhibitors
dickkopf & Cerberus
where are Wnt inhibitors made
by the dorsal anterior mesoderm
what are Wnt inhibitors important for, how do we know?
establishing neuroectodermal tissue
- ectopic placement of Cerberus results in the formation of a secondary head structure
where is FGF and RA found in high conc
FGF = posterior
RA = central mesoderm in the middle of the embryo
what do dorsal neurons of the spinal cord form
sensory neruons
what do ventral neurons of the spinal cord form
motor neurons
the anterior part of the neural tube divides rapidly to form three primary vesicles - what are they?
the forebrain midbrain and hindbrain
what part of the forebrain curls up to form a three pronged structure, what does it develop into
telencephalon - develops the cerebral cortex
what does the midbrain form
vision, hearing and motor control
what does the hindbrain form
cerebellum, medulla and pons
what do the first neurones to arrive in the pial surface form
the pre plate
when the first wave of cortical plate neurons arrive, they split the preplate into what 3 zones
marginal zone
cortical plate
subplate
how can neural stem cells be visualised
they express nestin - so using an anti-nestin antibody
how can radial glial fibres be visualised
they express vimentin - using a anti-vimentin antibody
what happens when migrating neurons detach from the radial glia
they translocate tangentially to their final position
what produces reelin
cajal-retzius cells of the marginal zone
what does reelin bind to
very low density lipoprotein receptor (VLDL-R), ApoER2 and integrin receptors
what happens when reelin binds
disabled 1 binds to the cytoplasmic tails of reelin receptors, and becomes phosophorylated = downstream signalling cascades result in gene expression and the surface properties of then neuron changing = causing them to migrate
what happens in reeler and scrambler mice
the preplate fails to split because neurones are unable to penetrate into it
what is doublecortin
a MAP expressed in migrating neurons - mutation to DCX results in poor neuronal migration and lissencephaly (in males) and double cortex syndrome (in females)
what is double cortex syndrome
half the cells have a functional copy of DCX and migrate correctly into a layered cortex
the other half do not migrate properly resulting in bands of grey matter between the ventricle and cortex
name 2 locations of adult stem cells
dentate gyrus
lining of lateral ventricles in the sub ventricular zone
name the 3 domains of the axonal growth cone
- central domain
- transitional domain
- peripheral domain
give an example of where semaphorin is expressed
the ventral part of the spinal cord secretes semaphorin 3 to repel thermoreceptor and noiceptor neurites
name a contact repulsant
ephrin
give an example of where ephrin is involved
retinotopic map formation = nerve cells in the retina send out projections to the tectum (superior colliculus in mammals) that directs eye movements.
Temporal retinal neurons have high sensitivity to ephrins (repelled). Nasal retinal neurons have low sensitivity to ephrins and so extend to a higher concentration of ephrins.
what factor is needed for neural survival
brain derived neurotrophic factor
describe a dystrophic defect
spinal bifida = the spinal cord and its meninges herniate through a defect in the vertebral column
- early surgical repair increases changes of survival
- affected infants can have motor and sensory deficits
describe lissencephaly
(lack of neural folds): brain surface is smooth due to failure of neuronal migration affected children have small brains and often develop intractable seizures, with severe impairment of neurological development
